Human interleukin 1 (IL-1) is a protein having a molecular weight of 20,000-25,000 and belonging to the family of the lymphomonokines, a plentiful group of proteins which modulate the immune functions.
Human interleukin 1, which is produced to a large extent by cells of the monocyte/macrophage line, appears to be one of the most significant stimulants of the T lymphocytes (Oppenheim, J. J. et al., Fed. Proc. 41, 257 (1982)).
IL-1 does in fact appear to contribute to the amplification of the immune response during the phase of recognition of the antigen, this taking place by means of an effect on the helper T lymphocytes and on the cytotoxic T lymphocytes.
Furthermore, IL-1 appears to be capable of carrying out multiple actions which are not specifically immunological but which, nevertheless, because they take place in the course of inflammation, may be ascribed to a different mechanism of protection which the host utilizes in order to overcome pathological conditions.
Among the various proinflammatory activities of IL-1, we shall mention the induction of fever, the induction of prostaglandin E.sub.2 and of proteins of the acute phase and the activation of neutrophils. Finally, IL-1 assists in the activation of repair mechanisms in the event of tissue damage, stimulating the growth of fibroblasts.
Having regard to its multiple activities, the possibility of using IL-1 as an immunomodulating drug has constantly become more attractive.
According to a process known in the art, interleukin 1 is produced by inducing secretion thereof by normal macrophages/monocytes of peripheral blood by means of the application of an inducing agent of bacterial origin.
However, this method presents difficulties such as the use of a large number of blood donors and a complex procedure for the separation of the monocytes.
French Patent Application No. 2,550,802 describes and claims a process for the production of interleukin 1 which comprises the culturing, in an appropriate culture medium, of a human leukemic cell line of haematopoietic origin and the induction of the secretion of interleukin 1 on the part of the said cells, by means of the application of inducing agents such as phorbols or esters thereof.
There then follows the separation of the interleukin 1 thus obtained from the culture medium and purification thereof by conventional methods. Nevertheless, this process is complicated by the numerous stages required and by the poor total yields, which reduce the attractiveness of the process itself from the industrial point of view.
There have recently been identified and cloned the genes which code for two proteins .alpha. and .beta. with IL-1 activity (Lomedico, P. T. et al.: Nature 312, 641 (1985); Auron, P. E. et al.: Proc. Natl. Acad. Sci, USA: 81, 7907 (1984)); March, C. J. et al.: Nature 315, 641 (1985)).
The use of the said genes for the preparation of heterolqgous proteins by the recombinant DNA technique does however present numerous problems.
In fact, operating according to the said technique leads on the one hand to the necessity for an accurate assessment of the possible risks which are generally associated with the introduction, into human therapy, of products obtained by means of genetic manipulations, and on the other hand to a situation in which there are difficulties in the production and purification of the desired proteins.
It has now been found that it is possible to overcome the difficulties of the known technique by means of a synthetic peptide with human interleukin 1 activity, which peptide can be used as a stimulant of the immune functions and as an adjuvant in vaccines and can be obtained in a pure form by a process which is simple and economically convenient.
The object of the present invention is accordingly to provide a synthetic peptide with human interleukin 1 activity, which peptide can be used as a stimulant of the immune functions and as an adjuvant in vaccines.
A further object of the present invention is to provide a process for the preparation thereof.
A yet further object of the present invention is constituted by the use of the said peptide for the preparation of pharmaceutical compositions which can be used to stimulate and/or to restore immune responses and as an adjuvant in the preparation of vaccines. Still further objects of the present invention will become evident from the description of the text and of the experimental examples which follow.